The overall objective of this grant is to study the role of epinephrine in the CNS control of blood pressure in the spontaneously hypertensive rat (SHR) and its appropriate control, the Wistar-Kyoto Rat (WKR). The EPI-containing neurons of the CNS of SHR and WKR will be studied by immunocytochemistry of phenylethanolamine-N-methyltransferase (PNMT) to determine whether there are differences in the numbers of cell terminals, cell numbers, cell sizes, or cell location between SHR and WKR. The levels of EPI and PNMT activity will be determined biochemically in these same areas. The relationship between the development of PNMT activity and the onset of hypertension will be studied. It has been established that intracerebroventricular (ICV) administration of EPI acts through a beta-adrenergic receptor to cause hypotension. The possibility that there are reduced numbers of beta-adrenergic receptors in the CNS or SHR vs. WKR will be determined by the analysis of the dissociation constants and numbers of beta-adrenergic receptors in SHR and WKR, first in whole brains and then in selected brain areas. The possibility that cyclic AMP is the mediator of the actions of EPI on the rat brainstem will be studied. The effect of EPI on cyclic AMP levels in areas of the rat brainstem which are postsynaptic to the EPI neurons localized by PNMT immunocytochemistry will be determined. The cyclic AMP dose-response curves to EPI will be compared in SHR and WKR to see if differences exist.